Inhibition of Amine Uptake

Inhibition of amine reuptake is believed to be the most important mechanism by which TCAs are efficacious in treating depression. TCAs are potent inhibitors of norepinephrine (NE) and serotonin (5-HT) reuptake but have little affinity for inhibition of dopamine (DA) reuptake. 3 Inhibition of neurotransmitter reuptake leads to increased synaptic levels and subsequent augmentation of the neurotransmitter response. Inhibition of NE reuptake is thought to produce the early sympathomimetic effects occasionally seen in some TCA overdoses and may contribute to the development of cardiac dysrhythmias. Serotonin syndrome results from increased 5-HT brainstem activity and has been produced by TCAs that are particularly potent 5-HT uptake inhibitors such as clomipramine and amitriptyline. In general, TCAs must be used in combination with other serotonergic agents to produce serotonin syndrome. Myoclonus and hyperreflexia often are attributed to increased serotonin activity.

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